Enantio‐ and Diastereoselective, Complete Hydrogenation of Benzofurans by Cascade Catalysis

Abstract

We report an enantio-and diastereoselective, complete hydrogenation of multiply substituted benzofurans in a one-pot cascade catalysis. The developed protocol facilitates the controlled installation of up to six new defined stereocenters and produces architecturally complex octahydrobenzofurans, prevalent in many bioactive molecules. A unique match of a chiral homogeneous ruthenium-N-heterocyclic carbene complex and an in situ activated rhodium catalyst from a complex precursor act in sequence to enable the presented process.

Haptophilicity and Substrate-Directed Reactivity in Diastereoselective Heterogeneous Hydrogenation

“…Supported metal nanoparticles are among the most important hydrogenation catalysts in the synthesis of complex organic molecules. − Because natural products and pharmaceutically relevant compounds frequently contain multiple stereocenters, any hydrogenation steps in their synthetic routes will require differentiation of diastereotopic faces of the organic molecule. − Heterogeneous catalysts typically favor hydrogenation from the less-hindered face of the organic compound due to the steric constraints of substrate adsorption onto the metal nanoparticle surface. − This inherent steric preference comes from the substrate structure itself and is difficult to alter through either catalyst or experimental parameters. In order to access counter-steric selectivity, one strategy is to incorporate a stereochemically defined functional group into the molecule that can coordinate to the catalyst surface and thereby “direct” hydrogen addition from the same face.…”

Rhodium‐Catalyzed Asymmetric Hydrogenation of All‐Carbon Aromatic Rings

“…Very recently, combining the advances in both fields of catalysis, an elegant cooperative homogeneous and heterogeneous catalytic AH of aromatic carbocyclic compounds has been reported (Figure 1B). Glorius and co‐workers discovered the complete hydrogenation of benzofurans could be achieved by using a distinctive combination of the chiral homogeneous Ru‐NHC complex and the in situ activated heterogeneous rhodium catalyst [9] . Soon afterward, a single rhodium complex, as both homogeneous and heterogeneous catalyst precursor was successfully used for AH of the vinylarenes by Andersson group [10] .…”

“…In the past few decades, considerable progress has been made in the field of homogeneous asymmetric hydrogenation (AH) of aromatic compounds, especially heteroarenes, [1–3] which provided an atom‐economical, straightforward and efficient route to the construction of the corresponding chiral cyclic compounds, and laid the good foundation for its application in pharmaceutical and agrochemical synthesis [4] . Compared with heteroarenes, the development of homogeneous AH of all‐carbon aromatic compounds was tardier due to the stronger aromaticity and the more difficult enantioselective control [5–10] . All the same, using the chiral N ‐heterocyclic carbene‐ruthenium catalyst (Ru‐NHC), the Glorius group reported the first site‐selective AH of the carbocyclic ring of 6‐alkyl‐2,3‐diphenyl‐quinoxalines, giving the chiral 5,6,7,8‐tetrahydroquinoxalines with up to 88 % ee [6] .…”

Asymmetric Full Saturation of Vinylarenes with Cooperative Homogeneous and Heterogeneous Rhodium Catalysis

“…Traditionally, the hydrogenation of arenes is achieved by using solid supported heterogeneous rhodium catalysts . In recent years, homogeneous precursors are more frequently used as an alternative that can form nanoparticles under the reaction conditions. − These nanoparticles showed higher reactivity and a larger functional group tolerance compared to solid supported metal catalysts. To date, a clear separation between homogeneous and heterogeneous rhodium-catalyzed hydrogenation exists.…”